BACKGROUND: The Cogstate Brief Battery (CBB) is a computerized cognitive test battery used commonly to identify cognitive deficits related to Alzheimer's disease (AD). However, AD and normative samples used to understand the sensitivity of the CBB to AD in the clinic have been limited, as have the outcome measures studied. OBJECTIVE: This study investigated the sensitivity of CBB outcomes, including potential composite scores, to cognitive impairment in mild cognitive impairment (MCI) and dementia due to AD, in carefully selected samples. METHODS: Samples consisted of 4,871 cognitively unimpaired adults and 184 adults who met clinical criteria for MCI (Clinical Dementia Rating (CDR) = 0.5) or dementia (CDR > 0.5) due to AD and CBB naive. Speed and accuracy measures from each test were examined, and theoretically- and statistically-derived composites were created. Sensitivity and specificity of classification of cognitive impairment were compared between outcomes. RESULTS: Individual CBB measures of learning and working memory showed high discriminability for AD-related cognitive impairment for CDR 0.5 (AUCs ∼ 0.79-0.88), and CDR > 0.5 (AUCs ∼ 0.89-0.96) groups. Discrimination ability for theoretically derived CBB composite measures was high, particularly for the Learning and Working Memory (LWM) composite (CDR 0.5 AUC = 0.90, CDR > 0.5 AUC = 0.97). As expected, statistically optimized linear composite measures showed strong discrimination abilities albeit similar to the LWM composite. CONCLUSIONS: In older adults, the CBB is effective for discriminating cognitive impairment due to MCI or AD-dementia from unimpaired cognition with the LWM composite providing the strongest sensitivity.

• Klíčová slova
• Alzheimer’s disease, cogstate brief battery, composites, dementia, discriminability, mild cognitive impairment,
• MeSH
• Alzheimerova nemoc * komplikace   diagnóza   psychologie   MeSH
• kognice MeSH
• kognitivní dysfunkce * diagnóza   psychologie   MeSH
• kognitivní poruchy * MeSH
• lidé MeSH
• neuropsychologické testy MeSH
• senioři MeSH
• senzitivita a specificita MeSH
• Check Tag
• lidé MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

Finding a cure for Alzheimer's disease (AD) has been notoriously challenging for many decades. Therefore, the current focus is mainly on prevention, timely intervention, and slowing the progression in the earliest stages. A better understanding of underlying mechanisms at the beginning of the disease could aid in early diagnosis and intervention, including alleviating symptoms or slowing down the disease progression. Changes in social cognition and progressive parvalbumin (PV) interneuron dysfunction are among the earliest observable effects of AD. Various AD rodent models mimic these early alterations, but only a narrow field of study has considered their mutual relationship. In this review, we discuss current knowledge about PV interneuron dysfunction in AD and emphasize their importance in social cognition and memory. Next, we propose oxytocin (OT) as a potent modulator of PV interneurons and as a promising treatment for managing some of the early symptoms. We further discuss the supporting evidence on its beneficial effects on AD-related pathology. Clinical trials have employed the use of OT in various neuropsychiatric diseases with promising results, but little is known about its prospective impacts on AD. On the other hand, the modulatory effects of OT in specific structures and local circuits need to be clarified in future studies. This review highlights the connection between PV interneurons and social cognition impairment in the early stages of AD and considers OT as a promising therapeutic agent for addressing these early deficits.

• Klíčová slova
• Alzheimer’s disease, animal models, dementia, hippocampus, oxytocin, parvalbumin interneurons, social cognition, social memory,
• MeSH
• Alzheimerova nemoc * patologie   MeSH
• hipokampus patologie   MeSH
• interneurony MeSH
• kognice MeSH
• lidé MeSH
• modely nemocí na zvířatech MeSH
• myši transgenní MeSH
• oxytocin MeSH
• parvalbuminy metabolismus   MeSH
• prospektivní studie MeSH
• sociální kognice MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• oxytocin MeSH
• parvalbuminy MeSH

BACKGROUND: Memory tests using controlled encoding and cued recall paradigm (CECR) have been shown to identify prodromal Alzheimer's disease (AD), but information about the effectiveness of CECR compared to other memory tests in predicting clinical progression is missing. OBJECTIVE: The aim was to examine the predictive ability of a memory test based on the CECR paradigm in comparison to other memory/non-memory tests for conversion to dementia in patients with amnestic mild cognitive impairment (aMCI). METHODS: 270 aMCI patients from the clinical-based Czech Brain Aging Study underwent a comprehensive neuropsychological assessment including the Enhanced Cued Recall test (ECR), a memory test with CECR, two verbal memory tests without controlled encoding: the Auditory Verbal Learning Test (AVLT) and Logical memory test (LM), a visuospatial memory test: the Rey-Osterrieth Complex Figure test, and cognitive testing based on the Uniform Data Set battery. The patients were followed prospectively. Conversion to dementia as a function of cognitive performance was examined using Cox proportional hazard models. RESULTS: 144 (53%) patients converted to dementia. Most converters (89%) developed dementia due to AD or mixed (AD and vascular) dementia. Comparing the four memory tests, the delayed recall scores on AVLT and LM best predicted conversion to dementia. Adjusted hazard ratios (HR) of immediate recall scores on ECR, AVLT, and LM were similar to the HR of categorical verbal fluency. CONCLUSION: Using the CECR memory paradigm in assessment of aMCI patients has no superiority over verbal and non-verbal memory tests without cued recall in predicting conversion to dementia.

• Klíčová slova
• Alzheimer’s disease, memory, mild cognitive impairment, verbal fluency,
• MeSH
• Alzheimerova nemoc * diagnóza   MeSH
• kognitivní dysfunkce * psychologie   MeSH
• krátkodobá paměť MeSH
• lidé MeSH
• neuropsychologické testy MeSH
• progrese nemoci MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: Considering the world's rapidly increasing life expectancy, with people working and maintaining active lifestyles longer than ever before, addressing the effects of aging on cognition is of utmost importance. A greater understanding of cognitive aging may also be critical in distinguishing natural cognitive aging from pre-clinical stages of Alzheimer's disease and related cognitive disorders. OBJECTIVE: To systematically examine the association between aging and cognitive performance in a cognitively and otherwise healthy probability population-based sample using a computer-based method. METHODS: This cross-sectional study enrolled 673 cognitively and otherwise healthy participants aged 25-89 years (mean age 52.3±14.2 years, 52.5% of whom were female) from the Kardiovize study cohort. Mild cognitive impairment and dementia cases were excluded, followed by measurement of cognitive performance with the computer-administered Cogstate Brief Battery. We used ANCOVA and Modified Signed-Likelihood Ratio tests to examine patterns of cognition across age groups. RESULTS: We found a gradual decrease in cognitive performance across the lifespan, which required two decades to demonstrate significant changes. In contrast to attention and learning, psychomotor speed and working memory showed the most significant age-related decrease and variability in performance. The established pattern of cognitive aging was not altered by sex or education. CONCLUSION: These findings corroborate, validate, and extend the current understanding of natural cognitive aging and pinpoint specific cognitive domains with the most extensive age-related interindividual differences. This will contribute to the development of strategies to preserve cognition with aging and may also serve to improve early diagnostics of cognitive disorders using computer-based methods.

• Klíčová slova
• Aging, Alzheimer’s disease, cognition, physiology, pre-clinical diagnostics,
• MeSH
• Alzheimerova nemoc * psychologie   MeSH
• kognice MeSH
• kognitivní dysfunkce * diagnóza   psychologie   MeSH
• lidé MeSH
• neuropsychologické testy MeSH
• průřezové studie MeSH
• senioři MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: While the gender/sex differences in neuropsychiatric symptoms in dementia population are well described, gender/sex differences in mild behavioral impairment (MBI) in dementia-free populations and the relationship to cognitive performance and to subsequent cognitive decline have not been studied. OBJECTIVE: We aimed to explore gender/sex differences in the association of MBI with the level of cognitive performance and its rate of decline in a dementia-free cohort. METHODS: We studied 8,181 older adults enrolled in the online PROTECT UK Study. MBI was assessed using the MBI Checklist and cognition was measured by digit span, paired associate learning, spatial working memory, and verbal reasoning. Statistical analysis was conducted using linear regression models and linear mixed-effects models. RESULTS: Out of 8,181 individuals (median age 63 years, 73% females), 11% of females and 14% of males had MBI syndrome. Females exhibited less often symptoms of decreased motivation (45% versus 36% in males), impulse dyscontrol (40% versus 44% in males; p = 0.001) and social inappropriateness (12% versus 15%; p < 0.001), while they showed more often symptoms of emotional dysregulation (45% versus 36%; p < 0.001). The associations of MBI domains with some measures of cognitive performance and decline were stronger in males than females, with the exception of the association of emotional dysregulation with the rate of cognitive decline in verbal reasoning, which was present exclusively in females. CONCLUSION: MBI may influence cognition to a greater extent in males than in females. We propose that predictors and biomarkers of dementia should consider gender/sex as an effect modifier.

• Klíčová slova
• Behavioral symptoms, cognition, dementia, gender differences, sex differences,
• MeSH
• kognice MeSH
• kognitivní dysfunkce * psychologie   MeSH
• kognitivní stárnutí * MeSH
• lidé MeSH
• neuropsychologické testy MeSH
• pohlavní dimorfismus MeSH
• senioři MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: The effectiveness of glucose-lowering drugs (GLDs) is unknown among patients with dementia. OBJECTIVE: To analyze all-cause mortality among users of six GLDs in dementia and dementia-free subjects, respectively. METHODS: This was a longitudinal open-cohort registry-based study using data from the Swedish Dementia Registry, Total Population Register, and four supplemental registers providing data on dementia status, drug usage, confounders, and mortality. The cohort comprised 132,402 subjects with diabetes at baseline, of which 11,401 (8.6%) had dementia and 121,001 (91.4%) were dementia-free. Subsequently, comparable dementia - dementia-free pairs were sampled. Then, as-treated and intention-to-treat exposures to metformin, insulin, sulfonylurea, dipeptidyl-peptidase-4 inhibitors, glucagon-like peptide-1 analogues (GLP-1a), and sodium-glucose cotransporter-2 inhibitors (SGLT-2i) were analyzed in the parallel dementia and dementia-free cohorts. Confounding was addressed using inverse-probability weighting and propensity-score matching, and flexible parametric survival models were used to produce hazard ratios (HR) and 95% confidence intervals (CI) of the association between GLDs and all-cause mortality. RESULTS: In the as-treated models, increased mortality was observed among insulin users with dementia (HR 1.34 [95%CI 1.24-1.45]) as well as in dementia-free subjects (1.54 [1.10-1.55]). Conversely, sulfonylurea was associated with higher mortality only in dementia subjects (1.19 [1.01-1.42]). GLP-1a (0.44 [0.25-0.78]) and SGLT-2i users with dementia (0.43 [0.23-0.80]) experienced lower mortality compared to non-users. CONCLUSION: Insulin and sulfonylurea carried higher mortality risk among dementia patients, while GLP-1a and SGLT-2i were associated with lower risk. GLD-associated mortality varied between dementia and comparable dementia-free subjects. Further studies are needed to optimize GLD use in dementia patients.

• Klíčová slova
• Antidiabetics, dementia, diabetes, hyperglycemia, mortality, propensity-score,
• MeSH
• demence * komplikace   MeSH
• diabetes mellitus 2. typu * komplikace   farmakoterapie   epidemiologie   MeSH
• glifloziny * terapeutické užití   MeSH
• glukagonu podobný peptid 1 MeSH
• glukosa MeSH
• hypoglykemika terapeutické užití   MeSH
• inzulin terapeutické užití   MeSH
• lidé MeSH
• sulfonylmočovinové sloučeniny terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• glifloziny * MeSH
• glukagonu podobný peptid 1 MeSH
• glukosa MeSH
• hypoglykemika MeSH
• inzulin MeSH
• sulfonylmočovinové sloučeniny MeSH

BACKGROUND: Older adults with subjective cognitive decline (SCD) are at an increased risk of progression to mild cognitive impairment (MCI) or dementia. However, few have examined the specific cognitive tests that are associated with progression. OBJECTIVE: This study examined performance on 18 neuropsychological tests among participants with SCD who later progressed to MCI or dementia. METHODS: We included 131 participants from the Czech Brain Aging Study that had SCD at baseline. They completed a comprehensive neuropsychological battery including cognitive tests from the Uniform Data Set 2.0 enriched by the verbal memory test Rey Auditory Verbal Learning Test (RAVLT) and Rey-Osterrieth Complex Figure Test (ROCFT). RESULTS: Fifty-five participants progressed: 53% to non-amnestic MCI (naMCI), 44% to amnestic MCI (aMCI), and 4% to dementia. Scoring one SD below the mean at baseline on the RAVLT 1 and RAVLT 1-5 was associated with 133% (RAVLT 1; HR: 2.33 [1.50, 3.62]) and 122% (RAVLT 1-5; HR: 2.22 [1.55, 3.16]) greater risk of progression to MCI or dementia over 3.84 years on average. Worse performance on the RAVLT 5, RAVLT 1-5, RAVLT 30, and ROCFT-Recall was associated with progression to aMCI whereas worse performance on the RAVLT 1, TMT B, and Boston Naming Test was associated with progression to naMCI. CONCLUSION: At baseline, lower verbal memory performance was most strongly associated with progression to aMCI whereas lower executive or language performance was most strongly associated with progression to naMCI.

• Klíčová slova
• Cognitive aging, immediate recall, subjective memory complaints, verbal memory,
• MeSH
• demence * diagnóza   MeSH
• kognice MeSH
• kognitivní dysfunkce * diagnóza   psychologie   MeSH
• lidé MeSH
• neuropsychologické testy MeSH
• senioři MeSH
• testy paměti a učení MeSH
• Check Tag
• lidé MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: Cholinergic deficit and medial temporal lobe (MTL) atrophy are hallmarks of Alzheimer's disease (AD) leading to early allocentric spatial navigation (aSN) impairment. APOEɛ4 allele (E4) is a major genetic risk factor for late-onset AD and contributes to cholinergic dysfunction. Basal forebrain (BF) nuclei, the major source of acetylcholine, project into multiple brain regions and, along with MTL and prefrontal cortex (PFC), are involved in aSN processing. OBJECTIVE: We aimed to determine different contributions of individual BF nuclei atrophy to aSN in E4 positive and E4 negative older adults without dementia and assess whether they operate on aSN through MTL and PFC or independently from these structures. METHODS: 120 participants (60 E4 positive, 60 E4 negative) from the Czech Brain Aging Study underwent structural MRI and aSN testing in real-space arena setting. Hippocampal and BF nuclei volumes and entorhinal cortex and PFC thickness were obtained. Associations between brain regions involved in aSN were assessed using MANOVA and complex model of mutual relationships was built using structural equation modelling (SEM). RESULTS: Path analysis based on SEM modeling revealed that BF Ch1-2, Ch4p, and Ch4ai nuclei volumes were indirectly associated with aSN performance through MTL (pch1 - 2 = 0.039; pch4p = 0.042) and PFC (pch4ai = 0.044). In the E4 negative group, aSN was indirectly associated with Ch1-2 nuclei volumes (p = 0.015), while in the E4 positive group, there was indirect effect of Ch4p nucleus (p = 0.035). CONCLUSION: Our findings suggest that in older adults without dementia, BF nuclei affect aSN processing indirectly, through MTL and PFC, and that APOE E4 moderates these associations.

• Klíčová slova
• Allocentric spatial navigation, apolipoprotein E, basal forebrain, entorhinal cortex, hippocampus, magnetic resonance imaging, prefrontal cortex,
• MeSH
• alely MeSH
• Alzheimerova nemoc * diagnostické zobrazování   genetika   MeSH
• atrofie MeSH
• cholinergní látky MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• pars basalis telencephali * diagnostické zobrazování   MeSH
• senioři MeSH
• Check Tag
• lidé MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• cholinergní látky MeSH

Cognitive impairment following SARS-CoV-2 infection is being increasingly recognized as an acute and possibly also long-term sequela of the disease. Direct viral entry as well as systemic mechanisms such as cytokine storm are thought to contribute to neuroinflammation in these patients. Biomarkers of COVID-19-induced cognitive impairment are currently lacking, but there is some limited evidence that SARS-CoV-2 could preferentially target the frontal lobes, as suggested by behavioral and dysexecutive symptoms, fronto-temporal hypoperfusion on MRI, EEG slowing in frontal regions, and frontal hypometabolism on 18F-FDG-PET. Possible confounders include cognitive impairment due to hypoxia and mechanical ventilation and post-traumatic stress disorder. Conversely, patients already suffering from dementia, as well as their caregivers, have been greatly impacted by the disruption of their care caused by COVID-19. Patients with dementia have experienced worsening of cognitive, behavioral, and psychological symptoms, and the rate of COVID-19-related deaths is disproportionately high among cognitively impaired people. Multiple factors, such as difficulties in remembering and executing safeguarding procedures, age, comorbidities, residing in care homes, and poorer access to hospital standard of care play a role in the increased morbidity and mortality. Non-pharmacological interventions and new technologies have shown a potential for the management of patients with dementia, and for the support of their caregivers.

• Klíčová slova
• Alzheimer’s disease, COVID-19, SARS-CoV-2, cognition, dementia,
• MeSH
• Alzheimerova nemoc * patofyziologie   psychologie   MeSH
• biologické markery analýza   MeSH
• COVID-19 komplikace   imunologie   psychologie   terapie   MeSH
• kognitivní dysfunkce * imunologie   patofyziologie   virologie   MeSH
• komorbidita MeSH
• lidé MeSH
• mozek * diagnostické zobrazování   metabolismus   patofyziologie   virologie   MeSH
• neuroimunomodulace imunologie   MeSH
• neurozobrazování metody   MeSH
• péče o pacienta MeSH
• postakutní syndrom COVID-19 MeSH
• SARS-CoV-2 MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• biologické markery MeSH

BACKGROUND: Several early-life factors have been associated with higher risk of developing dementia. It is unclear whether season of birth (SOB) can affect cognitive aging in older adults or not. OBJECTIVE: We aimed to study the association of SOB with the level of cognitive performance as well as with the rate of cognitive decline. METHODS: We studied 70,203 individuals who participated in the Survey of Health, Aging and Retirement in Europe. Cognition was measured with tests on verbal fluency and immediate and delayed recall. We assessed the association of SOB with the level of cognitive performance using multiple linear regression and with the rate of cognitive decline using linear mixed-effects models. RESULTS: When compared to individuals born in winter and adjusted for sociodemographic and health-related characteristics, being born in summer was associated with a higher level of delayed recall (B 0.05; 95%CI 0.01 to 0.09) and verbal fluency (B 0.15; 95%CI 0.00 to 0.29) and being born in fall with a higher level of immediate recall (B 0.04; 95%CI 0.01 to 0.08) and verbal fluency (B 0.15; 95%CI 0.01 to 0.29). Individuals born in summer had a higher yearly decline in delayed recall (B -0.005; 95%CI -0.009 to 0.000), while the scores in delayed recall in participants born in spring showed an inverse trend (B 0.005; 95%CI 0.000 to 0.010). CONCLUSION: Individuals born in winter seem to carry a life-long disadvantage in a lower level of cognitive performance; however, being born in winter does not seem to affect the rate of cognitive decline.

• Klíčová slova
• Aging, SHARE, cognition, epidemiology, season of birth,
• MeSH
• kognitivní dysfunkce psychologie   MeSH
• kognitivní stárnutí fyziologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• longitudinální studie MeSH
• prospektivní studie MeSH
• průřezové studie MeSH
• roční období * MeSH
• zdravotnické přehledy MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Geografické názvy
• Evropa MeSH